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Iron Heterogeneity in Early Active Multiple Sclerosis Lesions
Mylyne Tham1, Josa M Frischer2, Stephen D Weigand3
1Department of Anatomy, Physiology, and Pharmacology/Cameco MS Neuroscience Research Centre, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Annals of Neurology
|November 27, 2020
Summary
Iron accumulates differently in active lesions of multiple sclerosis (MS) subtypes. Immunopattern II MS lesions show higher iron in macrophages compared to immunopattern III, suggesting distinct disease mechanisms and potential for MRI-based differentiation.
Area of Science:
- Neuroimmunology
- Neuroinflammation
- Demyelinating Diseases
Background:
- Multiple sclerosis (MS) is a complex inflammatory demyelinating disease.
- Altered iron distribution in MS brains suggests iron's role in demyelination and neurodegeneration.
- The variation of iron quantity and distribution across different MS immunopatterns remains uncharacterized.
Purpose of the Study:
- To compare iron quantity and distribution in early active lesions of immunopattern II and III multiple sclerosis.
- To investigate the cellular localization of iron within these distinct MS lesion types.
Main Methods:
- Synchrotron X-ray fluorescence imaging, histology, and immunohistochemistry were employed.
- Archival autopsy and biopsy tissues from 21 MS patients were analyzed.
- Iron content and distribution were quantitatively assessed in early active lesions and surrounding white matter.
Main Results:
- Immunopattern II lesions exhibited significantly higher iron content (64% more) than immunopattern III lesions.
- Iron was predominantly localized to macrophages within immunopattern II lesions, with minimal iron found in macrophages of immunopattern III lesions.
- Iron levels in immunopattern III lesions were lower than in the surrounding periplaque white matter.
Conclusions:
- Iron distribution and content are heterogeneous in early active MS lesions, varying significantly between immunopattern II and III.
- Differential iron accumulation in macrophages suggests distinct pathogenic mechanisms underlying these MS immunopatterns.
- Findings support the development of iron-sensitive MRI techniques for non-invasively differentiating MS immunopatterns.
